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US6365612B2 - Benzosultam oxazolidinone antibacterial agents - Google Patents

Benzosultam oxazolidinone antibacterial agents Download PDF

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Publication number
US6365612B2
US6365612B2 US09/819,134 US81913401A US6365612B2 US 6365612 B2 US6365612 B2 US 6365612B2 US 81913401 A US81913401 A US 81913401A US 6365612 B2 US6365612 B2 US 6365612B2
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alkyl
compound
methyl
dihydro
benzisothiazol
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Expired - Fee Related
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US09/819,134
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US20010047018A1 (en
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Michael J. Genin
Fred L. Ciske
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Pharmacia and Upjohn Co
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Pharmacia and Upjohn Co
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Assigned to PHARMACIA & UPJOHN COMPANY reassignment PHARMACIA & UPJOHN COMPANY ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: CISKE, FRED L., GENIN, MICHAEL J.
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents

Definitions

  • the present invention relates to novel benzosultam oxazolidinones, specifically relates to N-substituted bicyclic benzosultam oxazolidinones; and their preparations. These compounds have potent antibacterial activities.
  • the oxazolidinone antibacterial agents are a novel synthetic class of antimicrobials with potent activity against a number of human and veterinary pathogens, including gram-positive aerobic bacteria such as multiply-resistant staphylococci and streptococci, anaerobic organisms such as bacteroides and clostridia species, and acid-fast organisms such as Mycobacterium tuberculosis and Mycobacterium avium.
  • the benzosultam oxazolidinones of the present invention may also possess activities against gram-negative organisms such as Haemophilus influenza and Moraxella catarrhalis.
  • U.S. Pat. No. 5,164,510 discloses 5′-indolinyloxazolidin-2-ones which are useful as antibacterial agents.
  • U.S. Pat. Nos. 5,036,092; 5,036,093; 5,039,690; 5,032,605 and 4,965,268 disclose aminomethyl oxazolidinyl aza cycloalkylbenzene derivatives useful as antibacterial agents.
  • the present invention provides a compound of formula I
  • R 1 is H, NH 2 , NHC 1-4 alkyl, C 1-4 alkenyl, OC 1-4 alkyl, SC 1-4 alkyl, (CH 2 ) i —C 3-6 cycloalkyl, or C 1-4 alkyl, optionally substituted with 1-3 F, 1-2 Cl or CN;
  • R 2 is H, C 1-12 alkyl optionally substituted with phenyl or CN, or C 2-12 alkyl substituted with OH, SH, NH 2 , —OC 1-6 alkyl, —NHC 1-6 alkyl, —NHCOC 1-6 alkyl, —NHSO 2 C 1-6 alkyl, —S(O) i C 1-6 alkyl, or one to three halo;
  • Y is O or S
  • M is —(CH 2 ) n —, wherein n is 1 or 2 and i is 0, 1, or 2.
  • the present invention also provides:
  • composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier,
  • the invention also contains novel intermediates and processes that are useful for preparing compounds of formula I.
  • alkyl, alkenyl, etc. refer to both straight and branched groups, but reference to an individual radical such as “propyl” embraces only the straight chain radical, a branched chain isomer such as “isopropyl” being specifically referred to.
  • C i-j indicates a moiety of the integer “i” to the integer “j” carbon atoms, inclusive.
  • C 1-7 alkyl refers to alkyl of one to seven carbon atoms, inclusive.
  • Warm-blooded animals refer to farm animal, companion animal or other type of animal.
  • halo refers to fluoro, chloro, bromo, or iodo
  • the compounds of the present invention are generally named according to the IUPAC or CAS nomenclature system.
  • R 1 is NH 2 , —OCH 3 , or C 1-4 alkyl.
  • R 1 is methyl, ethyl, or isopropyl.
  • a specific value for R 1 is methyl.
  • R 1 A specific value for R 1 is ethyl.
  • R 2 is C 1-6 alkyl.
  • R 2 is C 1-6 alkyl substituted with CN.
  • R 2 is benzyl
  • R 2 is C 2-6 alkyl substituted with OH, SH, NH 2 , F, —OC 1-6 alkyl, —NHC 1-6 alkyl, —NHCOC 1-6 alkyl, —NHSO 2 C 1-6 alkyl, —S(O) i C 1-6 alkyl, or one to three halo.
  • R 2 is methyl or methyl substituted with CN.
  • R 2 is ethyl substituted with fluoro or methoxy.
  • R 2 is —CH 2 CH 2 F.
  • a specific value for Y is sulfur.
  • a specific value for Y is oxygen.
  • n 1
  • optically active forms for example, by resolution of the racemic form by recrystallization techniques, by synthesis from optically-active starting materials, by chiral synthesis, or by chromatographic separation using a chiral stationary phase
  • Examples of the present invention are:
  • nitrobenzosultam 1 (can be obtained according to the methods described in J. Het. Chem. 1986, 23, 1645), is first converted to a sodium salt by treatment with a suitable base such as sodium bicarbonate.
  • a suitable base such as sodium bicarbonate.
  • the nitrogen at the 1-position can then be alkylated by treatment with a variety of alkylating agents including alkyl halides and heating in a suitable solvent such as DMF.
  • These compounds of general structure 2 can be reduced by catalytic hydrogenation in the presence of a suitable catalyst such as palladium on carbon in a suitable solvent such as ethyl acetate, THF, methanol or combinations thereof to afford 5-aminobenzosultams 3.
  • compositions of this invention may be prepared by combining acceptable carrier and, optionally, with pharmaceutically acceptable adjuvants and excipients employing standard and conventional techniques.
  • Solid form compositions include powders, tablets, dispersible granules, capsules, cachets and suppositories.
  • a solid carrier can be at least one substance which may also function as a diluent, flavoring agent, solubilizer, lubricant, suspending agent, binder, tablet disintegrating agent, and encapsulating agent.
  • Inert solid carriers include magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, cellulosic materials, low melting wax, cocoa butter, and the like.
  • Liquid form compositions include solutions, suspensions and emulsions.
  • solutions of the compounds of this invention dissolved in water and water-propylene glycol and water-polyethylene glycol systems, optionally containing suitable conventional coloring agents, flavoring agents, stabilizers and thickening agents.
  • the pharmaceutical composition is provided employing conventional techniques in unit dosage form containing effective or appropriate amounts of the active component, that is, the compounds of formula I according to this invention.
  • the quantity of active component that is the compound of formula I according to this invention, in the pharmaceutical composition and unit dosage form thereof may be varied or adjusted widely depending upon the particular application, the potency of the particular compound and the desired concentration. Generally, the quantity of active component will range between 0.5% to 90% by weight of the composition.
  • the compounds or pharmaceutical compositions thereof will be administered orally, topically, transdermally, and/or parenterally at a dosage to obtain and maintain a concentration, that is, an amount, or blood-level of active component in the animal undergoing treatment which will be antibacterially effective.
  • a concentration that is, an amount, or blood-level of active component in the animal undergoing treatment which will be antibacterially effective.
  • such antibacterially effective amount of dosage of active component will be in the range of about 0.1 to about 500, preferably about 1.0 to about 50 mg/kg of body weight/day. It is to be understood that the dosages may vary depending upon the requirements of the patient, the severity of the bacterial infection being treated, and the particular compound being used.
  • the initial dosage administered may be increased beyond the above upper level in order to rapidly achieve the desired blood-level or the initial dosage may be smaller than the optimum and the daily dosage may be progressively increased during the course of treatment depending on the particular situation. If desired, the daily dose may also be divided into multiple doses for administration, e.g., two to four times per day.
  • compositions for parenteral administration will generally contain a pharmaceutically acceptable amount of the compound according to formula I as a soluble salt (acid addition salt or base salt) dissolved in a pharmaceutically acceptable liquid carrier such as, for example, water-for-injection and a buffer to provide a suitably buffered isotonic solution, for example, having a pH of about 3.5-6.
  • a pharmaceutically acceptable liquid carrier such as, for example, water-for-injection and a buffer to provide a suitably buffered isotonic solution, for example, having a pH of about 3.5-6.
  • Suitable buffering agents include, for example, trisodium orthophosphate, sodium bicarbonate, sodium citrate, N-methylglucamine, L(+)-lysine and L(+)-arginine to name but a few representative buffering agents.
  • the compounds according to formula I generally will be dissolved in the carrier in an amount sufficient to provide a pharmaceutically acceptable injectable concentration in the range of about 1 mg/ml to about 400 mg/ml of solution.
  • the resulting liquid pharmaceutical composition will be administered so as to obtain the abovementioned antibacterially effective amount of dosage.
  • the compounds of formula I according to this invention are advantageously administered orally in solid and liquid dosage forms.
  • salts are organic acid addition salts formed with acids which form a physiological acceptable anion, for example, tosylate, methanesulfonate, acetate, citrate, malonate, tartarate, succinate, benzoate, ascorbate, (x-ketoglutarate, maleate, fumarate, benzenesulfonate and a-glycerophosphate.
  • Suitable inorganic salts may also be formed, including hydrobromide, hydrochloride, sulfate, nitrate, bicarbonate, and carbonate salts.
  • Step 1 Preparation of 1-methyl-5-nitro-1,3-dihydro-2H-2,1-benzisothiazole-2,2-dione:
  • Step 2 Preparation of N- ⁇ (2R)-2-hydroxy-3-[(1-methyl-2,2-dioxo-2,3-dihydro-1H-2,1-benzisothiazol-5-yl)amino]propyl ⁇ acetamide:
  • Step 1 The product of Step 1 (0.20 g, 0.88 mmol) is dissolved into EtOAc (30 mL) in a Parr bottle and 10% Pd/C (100 mg) added under nitrogen. The mixture is hydrogenated on a Parr apparatus for 2 hrs at 30 psi. Filtration and evaporation of solvent gave a white solid. This material is added to a mixture of N-[(2S)oxiranylmethyl] acetamide (0.81 g, 7.0 mmol) and magnesium trifluoromethanesulfonate (0.42 g, 1.3 mmol) in dry CH 3 CN (10 mL) at room temperature.
  • Step 1 Preparation of 1-(2-fluoroethyl)-5-nitro-1,3-dihydro-2H-2,1-benzisothiazole-2,2-dione
  • Step 2 Preparation of 5-amino-1-(2-fluoroethyl)-1,3-dihydro-2H-2,1-benzisothiazole-2,2-dione
  • Step 1 The product of Step 1 (1.25 g, 4.8 mmol) is dissolved into EtOAc (30 mL) in a Parr bottle and 10% Pd/C (100 mg) added under nitrogen. The mixture is hydrogenated on a Parr apparatus for 4 hrs at 40 psi. Filtration and evaporation of solvent gave a solid (1.1 g, 99%). Mp 119-21° C. HRMS (FAB) calcd for C 9 H 11 FN 2 O 2 S +H 1 231.0603, found 231.0610.
  • Step 3 N-( ⁇ (5S)-3-[1-(2-fluoroethyl)-2,2-dioxo-2,3-dihydro-1H-2,1-benzisothiazol-5-yl ⁇ -2-oxo-1,3-oxazolidin-5-yl]methyl)acetamide PNU-254380
  • N,N′-Disuccinimidyl carbonate (2.25 g, 9.0 mmol) is added followed by triethylamine (2.6 mL, 18.8 mmol) and the mixture stirred at room temperature for 20 hrs.
  • the mixture is poured into CH 2 Cl 2 (30 mL) and washed with H 2 O (3 ⁇ 20 mL).
  • the organics are dried (Na 2 SO 4 ), filtered and solvent evaporated.
  • the residue is chromatographed (3%MeOH/CH 2 Cl 2 ) to obtain a white solid (0.58 g, 38%). Mp 84-7° C. (dec).
  • HRMS (FAB) calcd for C 15 H 18 FN 3 O 5 S +H 1 372.1029, found 372.1021.
  • Step 2 N-( ⁇ (5S)-3-[1-(2-nitriloethyl)-2,2-dioxo-2,3-dihydro-1H-2,1-benzisothiazol-5-]-2-oxo-1,3-oxazolidin-5-yl ⁇ methyl)acetamide PNU-274919
  • Step 1 The product of Step 1 (0.73 g, 2.9 mmol) is dissolved into EtOAc (30 mL) in a Parr bottle and 10% Pd/C (100 mg) added under nitrogen. The mixture is hydrogenated on a Parr apparatus for 2 hrs at 40 psi. Filtration and evaporation of solvent gave a yellow solid which is added to a mixture of N-[(2S)oxiranylmethyl]acetamide (0.97 g, 8.0 mmol) and magnesium trifluoromethanesulfonate (1.3 g, 4.0 mmol) in dry CH 3 CN (30 mL) at room temperature. After 20 hrs solvent is evaporated and the residue chromatographed (4% MeOH/CH 2 Cl 2 ).
  • Step 2 N-( ⁇ (5S)-3-[1-(2-methoxyethyl)-2,2-dioxo-2,3-dihydro-1H-2,1-benzisothiazol-5-yl]-2-oxo-1,3-oxazolidin-5-yl ⁇ methyl)acetamide PNU-276461
  • Step 1 The product of Step 1 (0.70 g, 2.6 mmol) is dissolved into EtOAc (30 mL) in a Parr bottle and 10% Pd/C (100 mg) added under nitrogen. The mixture is hydrogenated on a Parr apparatus for 2 hrs at 40 psi. Filtration and evaporation of solvent gave a residue which is added to a mixture of N-[(2S)oxiranylmethyl]acetamide (0.115 g, 1.0 mmol) and magnesium trifluoromethanesulfonate (0.32 g, 1.0 mmol) in dry CH 3 CN (10 mL) at room temperature.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
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  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Oncology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Ophthalmology & Optometry (AREA)
  • Dermatology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
US09/819,134 2000-03-31 2001-03-27 Benzosultam oxazolidinone antibacterial agents Expired - Fee Related US6365612B2 (en)

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EP (1) EP1268475B1 (fr)
JP (1) JP2003529600A (fr)
KR (1) KR20020084274A (fr)
CN (1) CN1406237A (fr)
AR (1) AR035481A1 (fr)
AT (1) ATE277040T1 (fr)
AU (2) AU2001247540B2 (fr)
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CA (1) CA2399275A1 (fr)
DE (1) DE60105786T2 (fr)
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PE (1) PE20011124A1 (fr)
PT (1) PT1268475E (fr)
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6562979B1 (en) * 1999-07-16 2003-05-13 Basf Aktiengesellschaft Process for the preparation of substituted benzisothiazole compounds
US20100063277A1 (en) * 2007-05-04 2010-03-11 Zhang X Peter Intramolecular C-H amination with sulfonyl azides
US20110112288A1 (en) * 2008-03-31 2011-05-12 University Of South Florida Metal Porphyrin Catalyzed Olefin Aziridination with Sulfonyl Azides

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9928568D0 (en) 1999-12-03 2000-02-02 Zeneca Ltd Chemical compounds
GB0009803D0 (en) 2000-04-25 2000-06-07 Astrazeneca Ab Chemical compounds
US7012088B2 (en) * 2003-02-24 2006-03-14 Pharmacia & Upjohn Company Indolone oxazolidinones and derivatives thereof
DE102004026532A1 (de) 2004-05-29 2006-01-05 Sanofi-Aventis Deutschland Gmbh Substituierte Oxazol-Benzoisothiazoldioxidderivate, Verfahren zu deren Herstellung und deren Verwendung
WO2006106426A1 (fr) * 2005-04-06 2006-10-12 Pharmacia & Upjohn Company Llc Oxindole oxazolidinone utilise en tant qu'agent antibacterien

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US3704299A (en) * 1969-02-10 1972-11-28 Joseph A Skorcz 5-oxomorpholinyl-2,1-benzisothiazolines
US4965268A (en) 1987-10-09 1990-10-23 E. I. Du Pont De Nemours And Company Aminomethyl oxooxazolidinyl cycloalkylbenzene derivatives useful as antibacterial agents
US5032605A (en) 1987-10-09 1991-07-16 Du Pont Merck Pharmaceutical Company Aminomethyl oxooxazolidinyl oxa or thia cycloalkylbenzene derivatives useful as antibacterial agents
US5036093A (en) 1987-10-09 1991-07-30 Du Pont Merck Pharmaceutical Aminomethyl oxooxazolidinyl azacycloalkylbenzene derivatives useful as antibacterial agents
US5036092A (en) 1987-10-09 1991-07-30 Du Pont Merck Pharmaceutical Aminomethyl oxooxazolidinyl azacycloalkylbenzene derivatives useful as antibacterial agents
US5039690A (en) 1987-10-09 1991-08-13 Du Pont Merck Pharmaceutical Company Aminomethyl oxooxazolidinyl oxa or thia cycloalkylbenzene derivatives useful as antibacterial agents
US5164510A (en) 1988-09-15 1992-11-17 The Upjohn Company 5'Indolinyl-5β-amidomethyloxazolidin-2-ones
EP0738726A1 (fr) 1995-04-21 1996-10-23 Bayer Ag Hétérobenzocyclopentane oxazolidinones ayant une activité antibactérienne
US5684023A (en) 1994-07-20 1997-11-04 Bayer Aktiengesellschaft Benzofuranyl -and benzothienyloxazolidinones
WO1998032438A1 (fr) 1997-01-23 1998-07-30 Smithkline Beecham Corporation Antagonistes du recepteur de l'il-8
US5792765A (en) 1996-02-06 1998-08-11 Bayer Aktiengesellschaft Substituted oxazolidinones
WO1998034929A1 (fr) 1997-02-12 1998-08-13 Smithkline Beecham Corporation Antagoniste de recepteurs d'il-8
WO1999011264A1 (fr) 1997-09-05 1999-03-11 Smithkline Beecham Corporation Antagonistes du recepteur de l'il-8
WO1999036069A1 (fr) 1998-01-16 1999-07-22 Smithkline Beecham Corporation Antagonistes des recepteurs de l'interleukine-8
WO1999037641A1 (fr) 1998-01-22 1999-07-29 Bayer Aktiengesellschaft Nouvelles oxazolidinones a substitution bicyclene

Patent Citations (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3704299A (en) * 1969-02-10 1972-11-28 Joseph A Skorcz 5-oxomorpholinyl-2,1-benzisothiazolines
US4965268A (en) 1987-10-09 1990-10-23 E. I. Du Pont De Nemours And Company Aminomethyl oxooxazolidinyl cycloalkylbenzene derivatives useful as antibacterial agents
US5032605A (en) 1987-10-09 1991-07-16 Du Pont Merck Pharmaceutical Company Aminomethyl oxooxazolidinyl oxa or thia cycloalkylbenzene derivatives useful as antibacterial agents
US5036093A (en) 1987-10-09 1991-07-30 Du Pont Merck Pharmaceutical Aminomethyl oxooxazolidinyl azacycloalkylbenzene derivatives useful as antibacterial agents
US5036092A (en) 1987-10-09 1991-07-30 Du Pont Merck Pharmaceutical Aminomethyl oxooxazolidinyl azacycloalkylbenzene derivatives useful as antibacterial agents
US5039690A (en) 1987-10-09 1991-08-13 Du Pont Merck Pharmaceutical Company Aminomethyl oxooxazolidinyl oxa or thia cycloalkylbenzene derivatives useful as antibacterial agents
US5164510A (en) 1988-09-15 1992-11-17 The Upjohn Company 5'Indolinyl-5β-amidomethyloxazolidin-2-ones
US5684023A (en) 1994-07-20 1997-11-04 Bayer Aktiengesellschaft Benzofuranyl -and benzothienyloxazolidinones
EP0738726A1 (fr) 1995-04-21 1996-10-23 Bayer Ag Hétérobenzocyclopentane oxazolidinones ayant une activité antibactérienne
US5792765A (en) 1996-02-06 1998-08-11 Bayer Aktiengesellschaft Substituted oxazolidinones
WO1998032438A1 (fr) 1997-01-23 1998-07-30 Smithkline Beecham Corporation Antagonistes du recepteur de l'il-8
WO1998034929A1 (fr) 1997-02-12 1998-08-13 Smithkline Beecham Corporation Antagoniste de recepteurs d'il-8
WO1999011264A1 (fr) 1997-09-05 1999-03-11 Smithkline Beecham Corporation Antagonistes du recepteur de l'il-8
WO1999036069A1 (fr) 1998-01-16 1999-07-22 Smithkline Beecham Corporation Antagonistes des recepteurs de l'interleukine-8
WO1999037641A1 (fr) 1998-01-22 1999-07-29 Bayer Aktiengesellschaft Nouvelles oxazolidinones a substitution bicyclene

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6562979B1 (en) * 1999-07-16 2003-05-13 Basf Aktiengesellschaft Process for the preparation of substituted benzisothiazole compounds
US20100063277A1 (en) * 2007-05-04 2010-03-11 Zhang X Peter Intramolecular C-H amination with sulfonyl azides
US7956193B2 (en) 2007-05-04 2011-06-07 University Of South Florida Intramolecular C-H amination with sulfonyl azides
US20110112288A1 (en) * 2008-03-31 2011-05-12 University Of South Florida Metal Porphyrin Catalyzed Olefin Aziridination with Sulfonyl Azides

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CA2399275A1 (fr) 2001-10-11
DE60105786D1 (de) 2004-10-28
EP1268475A1 (fr) 2003-01-02
AU2001247540B2 (en) 2004-08-19
ZA200207003B (en) 2003-12-01
TR200402754T4 (tr) 2004-12-21
BR0108810A (pt) 2002-11-05
PT1268475E (pt) 2004-11-30
AU4754001A (en) 2001-10-15
EP1268475B1 (fr) 2004-09-22
ES2227166T3 (es) 2005-04-01
NZ521689A (en) 2004-05-28
AR035481A1 (es) 2004-06-02
KR20020084274A (ko) 2002-11-04
WO2001074812A1 (fr) 2001-10-11
CN1406237A (zh) 2003-03-26
DK1268475T3 (da) 2004-12-20
SI1268475T1 (en) 2005-02-28
JP2003529600A (ja) 2003-10-07
DE60105786T2 (de) 2006-02-23
MXPA02009317A (es) 2003-03-12
ATE277040T1 (de) 2004-10-15
PE20011124A1 (es) 2001-10-28
US20010047018A1 (en) 2001-11-29

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